The brief description of related technology provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventor, to the extent it is described in this brief description of related technology section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present disclosure.
Endomicroscopes perform optical sectioning and can collect in vivo images in the epithelium of hollow organs, such as colon, with sub-cellular resolution. This thin layer of tissue has high metabolic activity, and is the origin of many cancers. Under normal conditions, a vertical dimension (perpendicular to tissue surface) of the epithelium is approximately 400 μm in depth. Current clinical microscopes use a flexible optical fiber coupled to an objective lens in a single axis configuration. As a result, current clinical microscopes visualize solely in horizontal planes (i.e., parallel to tissue surface). However, imaging in the vertical plane is of great importance because epithelial cells naturally differentiate in this vertical direction. Additionally, cancer cells originate in this layer and invade downwards, thus a vertical view can provide the ability to accurately localize where the disease is occurring relative to the tissue surface, and pathologists could this orientation to stage progression of early cancer.
Imaging in the vertical plane benefits from an optical detection method with sufficient dynamic range to detect light over many orders of magnitude because of cumulative effects from tissue absorption and scattering. In some approaches, a dual axes confocal architecture is used that employs two distinct beams and objectives oriented off-axis to illuminate and collect light, and provide high dynamic range that rolls off exponentially in the axial (Z-axis) direction. Such designs use low numerical aperture objectives to produce a long working distance that provides space for a miniature scanner to be located in a post-objective position. This configuration allows for the optics to be scaled down to millimeter dimensions and to generate a very large field-of-view (FOV) compared to other endomicroscope designs, which have been used to demonstrate vertical cross-sectional images using a 10 mm diameter instrument with a large, bulky piezoelectric (PZT) actuator to perform axial scanning.
There is, however, an ongoing need for a miniature scanner that provides large angular deflections and sizable axial displacements to image in either the horizontal or vertical plane. Microscanners based on microelectromechanical systems (MEMS) technology have been developed and widely used in endomicroscopy. Yet, most MEMS scanners produce in-plane 2D scanning to only collect horizontal images. An actuator must either move the objective lens or scan out-of-plane to collect vertical images. Several MEMS-based 3D scanners have been developed that can enable tip-tilt-piston motions, but these devices suffer from coupling between different directions of motion and/or cannot reach as high scanning speeds as desired.
Other scanning technologies are being developed for use in endomicroscopes to perform in vivo imaging. While some designs can provide adequate lateral in vivo scanning, the designs have limitations in ability to scan with large out-of-plane displacement. Shape memory alloy (nitinol) based actuators, for example, are used in first generation confocal endomicroscopes to provide a large axial displacement (>250 μm), but these devices are slow and suffer from hysteresis. Other MEMS-based electrostatic scanners have been developed with fast response times at low voltages but have not achieved adequate Z-axis motion. Electrothermal devices can provide large axial displacements (>600 μm) at low voltages (˜5 V) but the response time is too slow for in vivo imaging. Piezoelectric scanners can achieve large DC displacements, but 3D fast-axis scanning frequencies are limited, and fabrication complexity is high. Electromagnetic scanners have been developed with fast response times and good displacement, but the technology is difficult to scale down in size for most endomicroscopy applications.